Membrane-bound blood group determinants have been characterized as being carried by sets of glycosphingolipids (e.g., Aa, Ab, Ac; H1, H2, H3, etc.) and by carbohydrate chains bound to the hydrophobic membrane proteins such as "band 3" protein. Alterations in the structure of the carrier portion as well as the terminal determinants are associated with development and with cancer. Specifically, we have detected a progressive branching of the carrier carbohydrate chain during development of erythrocytes. In human cancer, two types of significant changes in blood group determinants have been noticed; namely, the appearance in human cancer of incompatible blood group antigens foreign to the host, and the incomplete synthesis of blood group determinants and the associated accumulation of precursor chains. This application is to propose studies on: 1. Characterization of structure in detail and variation of the membrane-bound blood group ABH, Lewis, Ii and Forssman antigens and their carrier molecular species. Particular focus will be made on the determinants carried by gangliosides, polyglycosylceramides and hydrophobic membrane protein ("band 3" or alike). 2. Further studies on ontogenetic changes in blood group carrier carbohydrate chains and a possible change of Forssman antigens during ontogenesis of endodermal organs. 3. Chemical and immunological characterization of the "incompatible" blood group or Forssman isoantigens in human cancer and their corresponding isoantibodies present in normal and patients' sera. Particular emphasis will be the characterization of A-like antigen in tumors of O or B, and further extensive studies on Forssman antigen in tumors of F(negative) individuals in various cancers. 4. Enzymatic basis for synthesis of "incompatible" blood group and Forssman isoantigens and for the process of i to I or I to i conversion.